Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.Peer reviewe

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk

Abstract: In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene

Testing the effectiveness of the N-PALS model – a school-wide framework to prevent externalizing student problem behavior

Intervention effects on moderate and severe problem behavior in and outside the classroom context, on classroom climate and inclusion, and on perceived collective efficacy, self-efficacy, and disciplinary practices among the school staff were examined using a strengthened nonequivalent control group (NEC) design and multi-level analyses. Differential intervention effects were examined with implementation quality (fidelity), school size, program training dosage, or portion of untrained staff as moderators. Selected data from NUBUʼs (Norwegian Center for Child Development) longitudinal effectiveness and development study ʽPositive Behavior Support in Schoolʼ were used. This study involved totally 12,050 students (Grades 4-7), 3,695 teachers, after school personnel, and principals, and a random sample of 2,750 parents from 65 elementary schools around the country. Twenty-eight of the schools implemented the full-scale N-PALS model, 17 schools implemented the abbreviated version (PPBS), and 20 schools doing ʽpractice-asusual ʼ (PAU) made up the control group. The study was conducted over five successive school years. The analyses and results included in the dissertation are based on staff and student ratings from five of the totally six assessment points (double pre-test, two intermediate tests, post-test), and cover four of the five study years. The N-PALS model seemed effective in reducing the level of both moderate and severe externalizing student problem behaviors (particularly on common school areas) and in promoting qualitatively better social and academic learning conditions in class. The results also indicate increased ability in the intervention schools to reach out to all students and to reduce the number of students singled out for individual intervention plans due to conduct problems. N-PALS also appeared effective in promoting the school staffs’ perceived individual and collective efficacy. Besides, this three-level prevention framework appeared effective in changing staff behavior in positive ways. The schools with high implementation quality benefitted the most from the intervention model, and small-moderately sized schools reached higher implementation scores than large schools. Outcome analyses of the abbreviated PPBS intervention indicated promising immediate effects on several but not on all of the same outcome variables as the full threelevel model. Moderation analyses indicated better outcomes for schools with high fidelity scores, high mean training dosage, higher portion of untrained staff, and for small to medium sized schools. The significant effect sizes for the two intervention frameworks were generally large enough to be considered of practical significance, and the confidence intervals were narrow, indicating high precision of the estimates. The study results indicate that SWPBS was successfully transferred across the Atlantic without major adaptations, without violating the national curriculum or the norm of inclusion. The current study adds to the existing base of knowledge in several ways, including by being the first to examine the cumulative effects of the three-level model and by being the first effectiveness study of the SWPBS model implemented in Europe and in a non-English speaking context. Moreover, the Norwegian study is the first investigating effects of SWPBS/N-PALS on perceived teacher collective efficacy and on school staffs’ disciplinary practices, and also one of very few longitudinal effectiveness studies to date that have been conducted on this school-wide prevention model. Besides, our study is the first to investigate the relationship between collective efficacy and problem behavior in school, and on an empirical basis suggesting that teacher collective efficacy is a significant and reliable indicator of a school’s culture. Ideally, the study results should be replicated in a Scandinavian randomized controlled trial before more firm conclusions are drawn on the effectiveness of the N-PALS model

Postscript: Ogden, T. & Sørlie, M.A. (2009) Implementing and Evaluating Empirically Based Family and School Programmes for Children with Conduct Problems in Norway. International Journal of Emotional Education, 1(1), 96-107.

This postscript presents the implementation and evaluation of family and community based intervention programs for children and young people implemented in Norway. The Norwegian experiences and results illustrate how evidence-based programs developed in the US have been transported across geographical and language borders, implemented nationwide, evaluated for their effectiveness in regular practice and examined for sustainability. This update describes this national strategy, and the main components and immediate outcomes of the PMTO- and PALS-programs in Norway

Development of social skills during middle childhood: Growth trajectories and school-related predictors

This study examined the development of social skills across five measurement points from 4th through 7th grade, and the influence of child gender and school-related factors on the level and growth of social skills, in a large sample of normally developing children in Norway (N = 2,076). On average, children’s social skills scores increased slightly, girls received higher scores than boys, and individual order stability was fairly high over time. Growth mixture modeling (GMM) identified three distinct trajectory classes, one with stable average scores over time (72%), and two (14% each) with high initial and declining scores and low initial and increasing scores, respectively. The school-related factors (e.g., student–teacher relationships) predicted social skills development differently within the trajectory classes.publishedVersio

Environmental and temperamental correlates of alcohol user patterns in grade 7 students

AIMS – We examined the effects of temperamental dispositions, friends using alcohol and parental monitoring on grade 7 students’ alcohol use patterns

Development of social skills during middle childhood: Growth trajectories and school-related predictors

This study examined the development of social skills across five measurement points from 4th through 7th grade, and the influence of child gender and school-related factors on the level and growth of social skills, in a large sample of normally developing children in Norway (N = 2,076). On average, children’s social skills scores increased slightly, girls received higher scores than boys, and individual order stability was fairly high over time. Growth mixture modeling (GMM) identified three distinct trajectory classes, one with stable average scores over time (72%), and two (14% each) with high initial and declining scores and low initial and increasing scores, respectively. The school-related factors (e.g., student–teacher relationships) predicted social skills development differently within the trajectory classes

Examining Teacher Outcomes of the School-Wide Positive Behavior Support Model in Norway

Research on teacher outcomes of the School-Wide Positive Behavior Support (SWPBS) model has been scarce. The present study adds to the knowledge base by examining the effects of the Norwegian version of SWPBS (N-PALS) on school staffs’ behavior management practices and on their individual and collective efficacy. Questionnaire data were collected from staff and students (Grades 4-7) at four measurement points across four successive school years in 28 intervention schools and 20 comparison schools. Using longitudinal multilevel analyses, indications of positive 3-year main effects of the N-PALS model were observed for staff-reported collective efficacy, self-efficacy, and positive behavior support practices. The intervention effects as measured by Cohen’s d ranged from .14 to .91. The effects on student perceptions of teachers’ behavior management strategies were, however, not consistent with the positive staff ratings. Results are discussed in relation to prior research, future research, and study limitations

Impacts of school-wide positive behaviour support: Results from National Longitudinal Register Data

Problem behaviour in schools may have detrimental effects both on students' well‐being and academic achievement. A large literature has consistently found that school‐wide positive behaviour support (SWPBS) successfully addresses social and behavioural problems. In this paper, we used population‐wide longitudinal register data for all Norwegian primary schools and a difference‐in‐difference (DiD) design to evaluate effects of SWPBS on a number of primary and secondary outcomes, including indicators of externalising behaviour, school well‐being, pull‐out instruction, and academic achievement. Indications of reduced classroom noise were found. No other effects were detected. Analyses revealed important differences in outcomes between the intervention and control schools, independent of the implementation of SWPBS, and that a credible design like DiD is essential to handle such school differences

Heterogeneity in Short- and Long-Term Impacts of School-Wide Positive Behavior Support (SWPBS) on Academic Outcomes, Behavioral Outcomes, and Criminal Activity

To address social and behavioral problems in schools, more than 26,000 schools around the world have implemented School-Wide Positive Behavior Support (SWPBS). Previous studies have focused on the effects of SWPBS on short-term teacher-rated behavior such as office discipline referrals or academic outcomes, but no study has yet investigated effects on long-term student outcomes. We use population-wide longitudinal register data, including all Norwegian students that are exposed to SWPBS, and examine effects on short- and long-term academic outcomes, as well as long-term school behavior and youth crime. Both when we evaluate average program effects for all students and when looking at at-risk students only, we find no indications that the Norwegian SWPBS affected any of these outcomes